CD40 ligand inhibits Fas/CD95-mediated apoptosis of human blood-derived dendritic cells.
Dendritic cells (DC) are considered to be the most potent antigen-presenting cells (APC) in the immune system. In this study, we analyzed the regulation of apoptosis of human peripheral blood-derived DC. DC were generated from adherent peripheral blood mononuclear cells that had been cultured for 7 days with granulocyte-macrophage colony-stimulating factor and interleukin-4. These cells displayed phenotypic properties of DC, including dendritic processes, expression of CD1a and lack of expression of CD14, and were very potent at presenting soluble antigens to T cells. Blood-derived DC were demonstrated to express the Fas/CD95 antigen and an agonist antibody to CD95 strongly induced apoptotic cell death in these cells. Soluble trimeric CD40 ligand potently inhibited both CD95-mediated and spontaneous apoptosis in DC. The data suggest that interactions between members of the tumor necrosis factor family of ligands expressed by T cells with their receptors on DC play an important role in the regulation of apoptosis in DC during antigen presentation and may, therefore, regulate the duration of T cell expansion and cytokine production.
Koppi
T A
TA
Department of Microbiology, The University of Western Australia, Perth.
Tough-Bement
T
T
Lewinsohn
D M
DM
Lynch
D H
DH
Alderson
M R
MR
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D023201:CD40 Ligand; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D019014:fas Receptor / Q000276:immunology* / Q000494:pharmacology
D008562:Membrane Glycoproteins; D019014:fas Receptor; D023201:CD40 Ligand